Petition to Cancel Registration of Pnr1427 Insecticide (Brand Name Seresto)

BEFORE THE UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

PETITION TO CANCEL REGISTRATION OF PNR1427 INSECTICIDE (BRAND NAME SERESTO)

EPA REGISTRATION NO. 11556-155 (REGISTERED MAR. 16, 2012)

Reproduction from Aggregate Incident Summary Report for Seresto (June 16, 2020)

SUBMITTED BY: CENTER FOR BIOLOGICAL DIVERSITY APRIL 8, 2021

Via Electronic and Certified Mail

April 8, 2021

Michael Regan, Administrator U.S. Environmental Protection Agency 1200 Pennsylvania Ave. NW Mail Code: 1101A Washington, DC 20460 [email protected]

Michal Ilana Freedhoff, Acting Asst. Admin. Office of Chemical Safety and Pollution Prevention U.S. Environmental Protection Agency 1200 Pennsylvanian Avenue, N.W. Mail Code 7101M Washington, DC 20460 [email protected]

Edward Messina, Acting Director Office of Pesticide Programs U.S. Environmental Protection Agency 1200 Pennsylvania Ave. NW Mail Code: 7501P Washington, DC 20460 [email protected]

Re: Petition to Cancel Registration of PNR1427 (Brand Name Seresto) under the Federal Insecticide, Fungicide, and Rodenticide Act; Reg. No. 11556-155

Dear Administrator Regan, Acting Assistant Administrator Freedhoff, and Acting Director Messina,

Pursuant to the right to petition the government provided in the First Amendment to the U.S. Constitution1 and the Administrative Procedure Act,2 the Center for Biological Diversity—on behalf of itself and its 1.7 million members and supporters and their beloved companion

1 See U.S. Const. Amend. I; see also United Mine Workers v. Ill. State Bar Ass’n, 389 U.S. 217, 222 (1967) (explaining that the right to “petition for a redress of grievances [is] among the most precious of the liberties safeguarded by the Bill of Rights”). 2 See 5 U.S.C. § 553(e). 1 animals—hereby petitions the U.S. Environmental Protection Agency (EPA) to cancel its registration of insecticide product PNR1427, more commonly known by its brand name Seresto; Registration No. 11556-155. This product, which is registered under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) for use on adult dogs and puppies and on adult cats and kittens for the purpose of flea and tick treatment, poses a severe risk to the animals on which it is used and to human health. According to a recent aggregate incident summary report, since this product was introduced in 2012, EPA has received over 75,000 adverse incident reports, including at least 1,698 reports linking the use of this product to pet deaths and at least 700 involving human harm.3 Because these harms amount to significant unreasonable adverse effects under FIFRA, cancellation of this product is not only warranted but essential for protecting public health, consumers, imperiled wildlife, and companion animals. In the interim pending complete cancellation of the product, EPA should take additional steps to suspend Seresto’s registration.

I. PETITIONER

The Center for Biological Diversity (Center) is a non-profit environmental organization dedicated to the protection of native species and their habitats through science, policy, and environmental law. The Center has more than 1.7 million members and online activists dedicated to the protection and restoration of endangered species and wild places. For over 30 years, the Center has worked to protect imperiled plants and wildlife, open space, air and water quality, and overall quality of life. The Center’s Environmental Health Program and Pesticides Reduction Campaign aim to improve pesticide regulation in order to reduce the harms of pesticides to the environment, human populations, and threatened and endangered species.

II. ACTION REQUESTED

Because of the dangers posed by Seresto to threatened and endangered species, companion animals, and people, the Center hereby petitions EPA to:

(1) Cancel registration number 11556-155 pursuant to FIFRA § 136d(b); and (2) Suspend Seresto’ s registration pending completion of cancellation proceedings pursuant to FIFRA § 136d(c)(1).

III. LEGAL AND FACTUAL BASIS FOR PETITION

a. Federal Insecticide, Fungicide, and Rodenticide Act

FIFRA, 7 U.S.C. § 136 et seq., provides the framework for the federal regulation of pesticide distribution, sale, and use. The law is intended to prohibit the use of pesticides that cause unreasonable adverse effects on the environment.4 The Administrator of the EPA is responsible for carrying out the mandates of the Act. Pursuant to this obligation, the Administrator may limit the use of certain pesticides to prevent unreasonable adverse effects.5

3 See Exhibit A. 4 7 U.S.C. § 136a(a). 5 Id. §§ 136a(c)(5)-(6). 2

FIFRA defines a “pesticide” as “any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest[.]”6 When a pesticide is sold or distributed, it is generally referred to as a “pesticide product.” FIFRA generally prohibits the sale or distribution of a pesticide product unless it has first been “registered” under FIFRA Section 3 by EPA.7

EPA “issues a license, referred to as a ‘registration,’ for each specific pesticide product allowed to be marketed; the registration approves sale of a product with a specific formulation, in a specific type of package, and with specific labeling limiting application to specific uses.”8 In order for the EPA to evaluate an application for pesticide registration, an application must “describ[e] how the pesticide will be used, the claims made of its benefits, the ingredients, and a description of all tests and studies done and the results thereof, concerning the product’s health, safety, and environmental effects.”9

FIFRA Section 3(c)(5), “Approval of Registration,” provides that EPA can register a pesticide only if the agency determines that:

(A) its composition is such as to warrant the proposed claims for it; (B) its labeling and other material required to be submitted comply with the requirements of this subchapter; (C) it will perform its intended function without unreasonable adverse effects on the environment; and (D) when used in accordance with widespread and commonly recognized practice it will not generally cause unreasonable adverse effects on the environment.10

The term “unreasonable adverse effects on the environment” is further defined as "any unreasonable risk to man or the environment, taking into account the economic, social, and environmental costs and benefits of the use of any pesticide."11 When EPA applies this risk- benefit balancing test, it may only register a pesticide if it finds that the risks associated with the use of a pesticide are justified by the benefits of such use.12 In order to remain registered, a pesticide must continue to meet this risk-benefit standard, which EPA may reassess at any time.13

6 Id. § 136(u). 7 Id. § 136a(a). 8 69 Fed. Reg. 47,732, 47,733 (Aug. 5, 2004). 9 Pollinator Stewardship Council v. EPA, 806 F.3d 520, 523 (9th Cir. 2015). 10 7 U.S.C. § 136a(c)(5). 11 Id. § 136(bb); see also id. §§ 136a(a), 136a(c)(5)(c). 12 Washington Toxics Coal. v. Envtl. Prot. Agency, 413 F.3d 1024, 1032 (9th Cir. 2005) (explaining that FIFRA uses a “cost-benefit analysis to ensure that there is no unreasonable risk created for people or the environment from a pesticide.”). 13 Id. at 1033 (The “EPA retains discretion to alter the registration of pesticides for reasons that include environmental concerns.” (citing 7 U.S.C. §§ 136d(c)(1)-(2), 136(l)); see also Nat. Res. Defense Council v. Johnson, 422 F. Supp. 2d 105, 109 (D.D.C. 2006) (“The EPA uses numerous types of review processes to periodically reevaluate a registered pesticide's risks and benefits.” (citing Beyond Pesticides/Nat'l Coal. Against the Misuse of Pesticides v. Whitman, 294 F. Supp. 2d 1, 3 (D.D.C. 2003)). 3

After an applicant submits sufficient data for pesticide registration, EPA may grant “unconditional registration” under § 136a(c)(5). “Unconditional registration necessarily requires sufficient data to evaluate the environmental risks.”14 If an applicant has not submitted sufficient data to support unconditional registration, EPA may conditionally register the pesticide under certain limited circumstances.15

A pesticide product remains registered until EPA or the registrant cancels it pursuant to FIFRA Section 6.16 Under Section 6, if it appears to EPA that a registered pesticide has “unreasonable adverse effects on the environment” when “used in accordance with widespread and commonly recognized practice,” then EPA may undertake cancellation proceedings.17 Any interested person may petition EPA to cancel a registered pesticide product.18 EPA is required by the Administrative Procedure Act to resolve the petition “within a reasonable time.”19

b. Seresto Product Registration

EPA registered insecticide product PNR1427, more commonly known by its brand name Seresto, for use on March 16, 2012. The product was unconditionally registered in accordance with FIFRA Section 3(c)(5) for use on adult cats and kittens above 10 weeks of age, as well as adult dogs and puppies above 7 weeks of age.20 The product, which is dispensed in the form of a pet collar fastened around the neck, is intended to repel and kill ticks for 8 months, including deer ticks, blacklegged ticks, American dog ticks, brown dog ticks, Lone Star ticks, fleas, flea larvae, and lice.21 The registration number for this product is 11556-155.

c. Seresto Active Ingredients

Seresto is made up of a plastic band impregnated with insecticides that are released over time to coat the animal’s fur.22 It contains as active ingredients the neonicotinoid imidacloprid (10%) and the pyrethroid flumethrin (4.5%).23 Understanding each of these ingredients, alone and in combination, is important for understanding the toxicity and risks that their use in Seresto presents to dogs, cats, humans, and exposed threatened and endangered species.

14 Pollinator Stewardship Council, 806 F.3d at 523; see also 7 U.S.C. § 136a(c)(5) (listing the findings required for unconditional registration). 15 See 7 U.S.C. § 136a(c)(7). 16 Id. § 136d. 17 Id. § 136d(b). 18 40 C.F.R. § 154.10; Washington Toxics Coal. v. EPA, 413 F.3d at 1033. 19 5 U.S.C § 555(b). 20 EPA, Notice of Pesticide Registration, Reg. No. 11556-155 (2012), https://www3.epa.gov/pesticides/chem_search/ppls/011556-00155-20120316.pdf. 21 Id. 22 See EPA, Weighing Risks to Children from Dogs Wearing Seresto Collars (2016), https://www.epa.gov/sites/production/files/2017- 01/documents/weighing_risks_to_children_from_dogs_wearing_seresto-tm_collars.pdf. 23 Id. 4

i. Imidacloprid

Imidacloprid is a neonicotinoid pesticide. Neonicotionoids are understood to produce neuronal toxicities in insects via a common mechanism of action, that being the disruption of acetylcholine/nAChR signaling. According to EPA, “[i]midacloprid [is] in the N-nitroguanidine group of neonicotinoids (IRAC subclass 4A) along with clothianidin, thiamethoxam and dinotefuran. Its mode of action on target insects involves out-competing the neurotransmitter, acetylcholine for available binding sites on the nAChRs. At low concentrations, neonicotinoids cause excessive nervous stimulation and at high concentrations, insect paralysis and death will occur.”24

Neonicotinoids like imidacloprid are most well-known for the harms they cause to pollinator species, including threatened and endangered pollinators like the Poweshiek skipperling (endangered), Dakota skipper (threatened), and rusty patched bumble bee (endangered).25 These species are often exposed to neonicotinoids through a broad array of non-intended exposure pathways, including through agricultural and household uses of the pesticide. Laboratory studies have demonstrated that the neonicotinoid imidacloprid is, for example, “highly toxic to bumble bees.”26 Even sub-lethal exposure in bumble bees results in “reduced food consumption, reproduction, worker survival rates, and foraging activity.”27 Neonicotinoids are also toxic to solitary native bees such as blue orchard and alfalfa leafcutter bees, with direct effects including increased mortality rate with direct contact,28 as well as other native pollinators.29

Studies also confirm that small doses of imidacloprid can negatively affected the ability of songbirds to navigate.30 This is especially concerning for birds that may eat an imidacloprid- treated seed or other coated product, since consumption can cause direct mortality as well as sub-

24 EPA, Preliminary Terrestrial Risk Assessment to Support the Registration Review of Imidacloprid, at 11-12 (2017), https://www.regulations.gov/document/EPA-HQ-OPP-2008-0844-1256. 25 79 Fed. Reg. 63,672, 63,737 (Oct. 24, 2014); Szymanski, J., et al., Rusty Patched Bumble Bee (Bombus affinis) Species Status Assessment (2016), https://ecos.fws.gov/ServCat/DownloadFile/120109. 26 Jennifer Hopwood, et al., The Xerces Soc’y for Invertebrate Conservation, Are Neonicotinoids Killing Bees?, at vi (2012), http://cues.cfans.umn.edu/old/pollinators/pdf-pesticides/Are-Neonicotinoids-Killing- Bees_Xerces-Society.pdf; see also Barraud, A., et al., The Impact of Pollen Quality on the Sensitivity of Bumblebees to Pesticides, 105 Acta Oecologica 103552 (2020); Whitehorn, P. R., et al., Neonicotinoid Pesticide Reduces Bumble Bee Colony Growth and Queen Production, 336 Science 351–352 (2012); Feltham, H., Park, K., Goulson, D., Field Realistic Doses of Pesticide Imidacloprid Reduce Bumblebee Pollen Foraging Efficiency, 23 Ecotoxicology 317–323 (2014). 27 Jennifer Hopwood, et al., The Xerces Soc’y for Invertebrate Conservation, Are Neonicotinoids Killing Bees?, at vi (2012), http://cues.cfans.umn.edu/old/pollinators/pdf-pesticides/Are-Neonicotinoids-Killing- Bees_Xerces-Society.pdf. 28 Id. at 15. 29 Christoph Sandrock et.al., Sublethal Neonicotinoid Insecticide Exposure Reduces Solitary Bee Reproductive Success, 16 Agricultural & Forest Entomology 119 (2014), https://beyondpesticides.org/assets/media/documents/pollinators/documents/Sandrocketal2013_Subletha lneonicexposurereducessolitarybeereproductivesuccess_AgricForEnt.pdf. 30 Margaret Eng, et al., Imidacloprid and Chlorpyrifos Insecticides Impair Migratory Ability in a Seed- Eating Songbird, 7 Scientific Reports 15176, DOI:10.1038/s41598-017-15446-x (2017). 5 lethal effects, with a leading concern being harm to reproduction.31 According to a 2017 EPA Preliminary Terrestrial Risk Assessment of imidacloprid, a large bird (> 1kg) would only need to eat one imidacloprid-treated potato seed to nearly exceed the risk of concern for acute harm and possible death.32

While most frequently associated with agricultural crop uses, imidacloprid is also the most common neonicotinoid used in household products, including flea and tick treatments such as Seresto. According to public records obtained from EPA by the Natural Resources Defense Council (NRDC), over the past decade there have been at least 1,630 recorded imidacloprid poisoning incidents in humans that are attributable to these uses.33 The reported symptoms include skin rash, muscle tremor, difficulty breathing, vomiting, wheezing, lock jaw, memory loss, and renal failure.34

This follows closely with EPA’s own findings about the health risks of imidacloprid to mammals—the class of vertebrates that includes humans, cats, and dogs. “The nervous system is the primary target organ of imidacloprid.”35 In early human health risk assessments of imidacloprid, EPA scientists noted a number of toxic effects in oral studies of rats and mice (surrogates for humans) from dietary exposure to imidacloprid.36 These effects included decreased movement and body weights, tremors, thyroid effects, retinal atrophy, and brain effects.37

Hitting even closer to concerns related to the use of imidacloprid as an active ingredient in Seresto, in a 2017 risk assessment EPA noted that dogs were more sensitive to imidacloprid than the standard test animals (e.g., rats and mice), even at doses seven times lower than the level of

31 See Ertl, H. et al., Potential Impact of Neonicotinoid Use on Northern bobwhite (Colinus virginianus) in Texas: A Historical Analysis, PLoS ONE 13:e0191100 (2018), https://doi.org/10.1371/journal.pone.0191100; Millott et al., Field Evidence of Bird Poisonings by Imidacloprid-Treated Seeds: A Review of Incidents Reported by the French SAGIR Network from 1995 to 2014, Environ Sci Pollut Res, DOI 10.1007/s11356-016-8272y (2016); Lopez-Antia et al., Risk Assessment of Pesticide Seed Treatment for Farmland Birds Using Refined Field Data, 136 Environmental Research 97 (2015). 32 EPA, Preliminary Terrestrial Risk Assessment to Support the Registration Review of Imidacloprid, (2017), https://www.regulations.gov/document/EPA-HQ-OPP-2008-0844-1256. 33 EPA, FOIAOnline, Request No. EPA-HQ-2019-004044 (2019), https://foiaonline.gov/foiaonline/action/public/submissionDetails?trackingNumber=EPA-HQ-2019- 004044&type=request; see also NRDC, Neonicotinoid Pesticides: Potential Risks to Brain and Sperm (Jan. 6, 2021), https://www.nrdc.org/experts/jennifer-sass/neonic-pesticides-potential-risks-brain-and- sperm#:~:text=Imidacloprid%20is%20the%20most%20common,by%20EPA%20(see%20here). 34 Id. 35 EPA, Preliminary Health Effects Division Risk Assessment for Imidacloprid, at 13 (2003), https://www3.epa.gov/pesticides/chem_search/cleared_reviews/csr_PC-129099_4-Mar-03_111.pdf. 36 Id. 37 Id. 6 toxicity for mice and rats.38 The neurotoxic effects consisted of severe tremors and trembling at mid- to high-doses.39 Acute oral toxicity studies in dogs were not further discussed.

The studies reviewed by EPA in generating these human health assessments were based on industry-generated studies and did not include the many published, peer-reviewed studies that have shown toxic effects in mammals from exposure to imidacloprid. The state of California, however, also conducted a human health risk assessment for imidacloprid that took a deeper look at the science around harms to health related to imidacloprid exposure through dietary and drinking water routes. That assessment, conducted by the California Environmental Protection Agency, emphasized that acute oral exposure of rats and mice to imidacloprid produced clinical signs that are similar to nicotine intoxication, including tremors, decreased coordination and mobility, spasms, respiratory difficulties, and lethargy.40 Even further, in longer term toxicity studies (subchronic and chronic), rats exposed to imidacloprid experienced body weight reductions.41 In the subchronic studies, the liver was the principal target organ with necrosis or toxic injury occurring in the liver.42 Additional effects noted in these studies included degeneration of the testes, atrophy of the thyroid gland and bone marrow, and effects on the thymus.43 In the chronic toxicity studies, reduction in body weight was a common toxic effect along with thyroid lesions in rats.44

In the two dog oral studies reviewed by California toxicologists, toxic effects from exposure to imidacloprid were observed in the liver, testes, thyroid, bone marrow, and thymus.45 Severe tremors were also reported in these studies.46 No cat-specific studies were analyzed.

For humans, the California assessment also specifically identified pregnant women or women of childbearing age as a high-risk group, finding that: “[e]vidence from the developmental neurotoxicity study in rats, suggested that imidacloprid may affect the neural development. The estimated NOEL for decreases in dimensions of brain structures was 5.5 mg/kg/day. This ENEL might be pertinent to acute exposures of women of childbearing age to protect for fetal exposure. Based on the ENEL of 5.5 mg/kg/day, the acute dietary MOEs for females 13-49 yrs. would be 366 at the 95th and 239 at 99th percentiles, which exceed the general health protective benchmark MOE of 100.”47 Further, and more generally, the assessment identified that:

Several human neuropathologies have been linked to genetic alterations of nAChRs genes or autoimmune disruption of the receptor proteins, including congenital

38 EPA, Imidacloprid: Human Health Draft Risk Assessment for Registration Review, at 11-12 (2017), https://www.regulations.gov/document?D=EPA-HQ-OPP-2008-0844-1235. 39 Id. at 14. 40 Cal. EPA, Imidacloprid: Risk Characterization Document; Dietary and Drinking Water Exposure, at ix (2006), https://www.cdpr.ca.gov/docs/risk/rcd/imidacloprid.pdf. 41 Id. 42 Id. 43 Id. 44 Id. 45 Id. at 61. 46 Id. 47 Id. at xii. 7

myasthenia, autosomal dominant frontal lobe nocturnal epilepsy and possibly a schizophrenic syndrome. These receptors are also involved at various degrees in several neuropathologies such as Parkinson and Alzheimer’s diseases, and Gilles de la Tourette’s syndrome. Autoimmune responses to specific neuronal nAChR subunits have been found in the skin disease pemphigus, in which cells of the epidermis lose adherence.48

Furthermore, a systematic review of peer-reviewed literature on human health effects of neonicotinoids reported a link between neonicotinoid exposures and malformations of the developing heart and brain, as well as a cluster of symptoms including memory loss and finger tremors.49 For example, the review discussed a study by National Institute of Health-funded researchers from University of North Carolina at Chapel Hill and University of California, Davis that associated frequent exposure to imidacloprid applied as flea and tick treatments for pets (Advantage by Bayer) during pregnancy with a 2-fold elevated risk of autism spectrum disorder in prenatally-exposed children.50

ii. Flumethrin

The other active ingredient found in Seresto pet collars, at 4.5%, is flumethrin. Flumethrin is a pyrethroid insecticide, which is in a class of pesticides that—like neonicotinoids—target insects’ peripheral and central nervous systems.51 These chemicals are some of the most widely used pesticides in the United States, both in agricultural and residential settings.52 Dependency on pyrethroids has increased over the past twenty years, propelled by interest in replacing organophosphate insecticides.53 Today, pyrethroids and pyrethrins are so heavily used that their environmental concentrations exceed regulatory thresholds.54

Until recently, pyrethroids were believed to have limited toxicity in humans; this belief was based on the assumption that they are rapidly metabolized by the human body. But current studies and scientific investigations cast serious doubt on that assumption. For example, one recent pharmacokinetic study on the pyrethroid deltamethrin indicates that its peak concentration in the human brain is two times higher than that in rats.55 Additionally, mammalian studies showed that repeated exposure to low levels of a pyrethroid insecticide caused learning

48 Id. at 3-4 (citations omitted). 49 Cimino, et al., Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review, 125(2) Environmental Health Perspectives 155 (2017), https://ehp.niehs.nih.gov/doi/full/10.1289/EHP515. 50 Id. at 160 (citing Keil, et al., Autism Spectrum Disorder, Flea and Tick Medication, and Adjustments for Exposure Misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) Control Study, 13 Environ. Health 3 (2014), https://pubmed.ncbi.nlm.nih.gov/24456651/). 51 T.G.E. Davies et al., DDT, Pyrethrins, Pyrethroids and Insect Sodium Channels, 59 LIFE 151, 155 (2007). 52 Muhammad M. Hossain, et al., Hippocampal ER Stress and Learning Deficits Following Repeated Pyrethroid Exposure, 143 Toxicological Sciences 220, 220 (2015). 53 Holly A Rogers, et al., Bifenthrin Causes Trophic Cascade and Altered Insect Emergence in Mesocosms: Implications for Small Streams, 50 Envtl. Sci. & Tech. 11,974, 11,974 (2016). 54 Id. 55 Stephen J. Godin, et al., Physiologically Based Pharmacokinetic Modeling of Deltamethrin: Development of a Rat and Human Diffusion-Limited Model, 115 Toxicological Sciences 330, 338 (2010). 8 deficiencies and physiological effects associated with neurodegeneration, Alzheimer’s, and Parkinson’s diseases, among others.56 Even further, one study revealed higher incidences of autism spectrum disorders and developmental delay amongst children whose mothers were living within 1.5 kilometers of sites of pyrethroid applications during the third trimester of pregnancy.57

EPA’s 2012 human health risk assessment of flumethrin for use in cat and dog collars indicates that it has toxic effects similar to many other pyrethroids.58 These effects include pawing, burrowing, writhing, salivation, coarse tremors, decreased body weights, and impaired motor activity.59 While a later 2018 human health risk assessment for flumethrin did not find risks of concern, it showed that the relevant toxicity studies were conducted on rats and mice rather than dogs or cats (the animals that the manufacturer of flumethrin was seeking approval for its use on), making it difficult to determine the actual toxic effects of flumethrin on dogs and cats.60

Further, according to a 2019 risk assessment of flumethrin, EPA identified that between 2013 and 2018 there were at least 907 incidents reported for humans.61 The assessment further determined that there were 19 severe incidents, with the most often reported symptoms being dermal (8 total) and neurological (7 total).62 Of the 8 people that experienced dermal incidents, the symptoms reported included rashes, skin lesions, and hives; of the 7 people that experienced neurological incidents, the symptoms reported included numbness, headaches, and seizures.63

A sampling of the incidents listed in that 2019 risk assessment include:

- A 12-year-old boy who slept in a bed with a dog wearing a collar started having seizures and vomiting. He had to be hospitalized.64 - A 67-year-old woman who slept in a bed with a dog wearing a collar reported having heart arrhythmia and fatigue.65 - A 43-year-old man put collars on eight dogs and slept in the same bed as four of the dogs. A week later, he developed ear drainage and nasal and throat irritation and was told by a

56 Muhammad M. Hossain, et al., Hippocampal ER Stress and Learning Deficits Following Repeated Pyrethroid Exposure, 143 Toxicological Sciences 220, 220 (2015). 57Janie F. Shelton, et al. Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study, 122 Children’s Health 1103, 1107 (2014). 58 See generally EPA, Flumethrin: Human Health Risk Assessment for the Section 3 Registration Action for Cat and Dog Collars (2016), https://www.regulations.gov/document?D=EPA-HQ-OPP-2016-0031- 0005. 59 Id. at 5. 60 EPA, Flumethrin: Draft Human Health Risk Assessment for Registration Review (2018), https://www.regulations.gov/document?D=EPA-HQ-OPP-2016-0031-0027. 61 EPA, Flumethrin: Tier I Update Review of Humane Incidents and Epidemiology for Proposed Interim Decision, at 3-4 (2019), https://www.regulations.gov/document/EPA-HQ-OPP-2016-0031-0031. 62 Id. at 4. 63 Id. 64 Id. at 8-9. 65 Id. at 8. 9

doctor that he had a hole in his ear drum. He removed the dog collars and the symptoms went away. He later reapplied the collars and the symptoms returned.66

Not only do pyrethroids present serious risks to the health of humans, dogs, and cats, but they also present risks to wildlife resources and ecosystems. A study by U.S. Geological Survey scientists found that commonly used pyrethroids have the potential to “alter aquatic and terrestrial ecosystem function at the regional scale.”67 More specifically, the study concluded that pyrethroid contamination in freshwater streams resulted in “less abundant and less diverse macroinvertebrate communities.”68 Additionally, the study revealed that pyrethroid contamination in aquatic ecosystems “propagate across life stages and generations of invertebrates, trophic levels in aquatic food webs, and ecosystem boundaries to riparian food webs.”69 Indeed, in its recent aquatic risk assessment for 20 pyrethroids and pyrethrins, EPA did an analysis on many of the home uses of this pesticide class and found significant risks to aquatic invertebrates from just the indoor uses alone.70

iii. The Synergistic Action of Imidacloprid and Flumethrin

Since imidacloprid and flumethrin do not exist in isolation in the Seresto product, their synergistic effects must also be taken into consideration. “Synergy” is the mixing of pesticide ingredients with other pesticides and chemicals before application (or after), and the ways in which the individual ingredients can interact in the mixture in a way that enhances their toxic effects. These synergies, which are generally not assessed by EPA when it approves a pesticide product and specifically were not assessed in its approval of Seresto,71 can turn what would normally be considered a safe level of exposure to people, wildlife, and the environment into one that causes considerable harm.72 However, even published studies by the original manufacturer of Seresto, Bayer, have shown that the combination of imidacloprid and flumethrin produces synergistic action in dogs and cats that may make these two chemicals more powerful and more toxic together than each individual pesticide alone.73

66 Id. 67 Holly A Rogers, et al., Bifenthrin Causes Trophic Cascade and Altered Insect Emergence in Mesocosms: Implications for Small Streams, 50 Envtl. Sci. & Tech. 11,974, 11,974 (2016). 68 Id. at 11,979. 69 Id. at 11,980. 70 EPA, Preliminary Comparative Environmental Fate and Ecological Risk Assessment for the Registration Review of Eight Synthetic Pyrethroids and the Pyrethrins, (2016), https://www.regulations.gov/document/EPA-HQ-OPP-2010-0384-0045. 71 EPA, Weighing Risks to Children from Dogs Wearing Seresto Collars (2016), https://www.epa.gov/sites/production/files/2017- 01/documents/weighing_risks_to_children_from_dogs_wearing_seresto-tm_collars.pdf (“The risk of the combination of the two active ingredients, flumethrin and imidacloprid, was not assessed . . . .”). 72 Nathan Donley, Center for Biological Diversity, Toxic Concoctions: How the EPA Ignores The Dangers of Pesticide Cocktails, 1 (2016), https://www.biologicaldiversity.org/campaigns/pesticides_reduction/pdfs/Toxic_concoctions.pdf. 73 Stanneck, et al., The Synergistic Action of Imidacloprid and Flumethrin and Their Release Kinetics From Collars Applied for Ectoparasite Control in Dogs and Cats, 5 Parasites & Vectors 73 (2012), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361670/. 10

Even further, as it relates to these two pesticides, recent research published by the journal Science has determined that neonicotinoids and pyrethroids have driven an increase in the toxicity of pesticides to aquatic invertebrates and pollinators, even as effects have generally fallen for vertebrates.74 As summarized by the researchers who conducted the study, "[o]ur results challenge the claims of a decrease in the environmental impacts of pesticide use."75

IV. STATEMENT OF LEGAL GROUNDS

FIFRA provides the legal framework for federal regulation of pesticide use, sale, and distribution. The law is intended to prohibit the use of pesticides that cause unreasonable adverse effects on the environment. EPA, the recipient of this petition, is responsible for carrying out the mandates of the Act. As identified through Exhibits A-C and supra in Section III (b) – (c), evidence exists that past and present uses of Seresto have caused unreasonable adverse impacts upon the environment and present an imminent hazard. The harms caused by Seresto use are not outweighed by the benefits of continued use. Therefore, pursuant to its obligations under FIFRA, EPA must cancel registration number 11556-155 pursuant to Section 136d(b) in order to prevent any additional unreasonable adverse effects on the environment, and, pending completion of cancellation proceedings, must suspend Seresto’s registration pursuant to Section 136d(c)(1).

a. Seresto Must be Cancelled for Causing an “Unreasonable Risk” to Man and the Environment in Violation of FIFRA

Cancellation of a pesticide product’s registration is warranted where the pesticide, “when used in accordance with widespread and commonly recognized practice, generally causes unreasonable adverse effects on the environment,” including “any unreasonable risk to man or the environment.”76 Here, the registration of Seresto must be cancelled because its continued use as a flea and tick collar for dogs and cats—which is the use for which is has been approved, and is therefore appropriately identified as use “in accordance with widespread and commonly recognized practice”—is causing unreasonable adverse effects on members of the public, imperiled species, and companion animals.

According to a recent aggregate incident summary report, since Seresto was introduced in 2012, EPA has received over 75,000 adverse incident reports on this product, including at least 1,698 reports linking the use of this product to pet deaths and nearly 700 involving harm humans.77 In addition, use of the collar has caused rashes, seizures, motor dysfunction, fatigue, diarrhea, vomiting, and excessive drooling in animals.78 According to Karen McCormack, a former

74 Schulz, Applied Pesticide Toxicity Shifts Toward Plants and Invertebrates, Even in GM Crops, 372 Science 81-84 (2021), https://science.sciencemag.org/content/372/6537/81. 75 Marc Heller, Farm Chemicals Turning More Toxic for Wildlife, E&E News (Apr. 1, 2021), https://www.eenews.net/eenewspm/stories/1063729071/feed. 76 7 U.S.C. § 136d(b); see also id. § 136(bb) (providing that “[t]he term ‘unreasonable adverse effects on the environment’ means (1) any unreasonable risk to man or the environment, taking into account the economic, social, and environmental costs and benefits of the use of any pesticide ….”). 77 See Exhibit A. 78 Jimy Tallal, Seresto Flea Collar Linked to 1,700 Pet Deaths, The Malibu Times (Mar. 26, 2021), http://www.malibutimes.com/news/article_36818990-8db8-11eb-9bf9-cf20318319cf.html; see also 11 pesticide researcher, policy analyst, environmental fate scientist, and communications specialist for EPA, Seresto collars “have the most incidents of any pesticide product she’s ever seen.”79

For comparison, in 2009 NRDC petitioned EPA to cancel all pet uses for the pesticide tetrachlorvinphos (TCVP) due to the risks it posed to the health of children and because EPA relied on a faulty health assessment in approving its use in flea collars and powders.80 In 2020, in response to a legal challenge brought by NRDC against EPA’s for its delay in responding to the 2009 petition, the Ninth Circuit Court of Appeals issued a decision highlighting the gravity of these risks and finding that “[r]epeatedly, the EPA has kicked the can down the road and betrayed its prior assurances of timely action, even as it has acknowledged that the pesticide poses widespread, serious risks to the neurodevelopmental health of children.”81 Yet, even in that case the number of incidents related to the use of TCVP (approximately 4,600, including 363 deaths, between 1992 and 2008) paled in comparison to those being reported for Seresto (75,000, including almost 1,700 deaths).82

Further, in the case of TCVP, one of the primary concerns expressed in that petition was that:

These products are designed to leave chemical residues on a pet's fur. Children playing with their cat or dog get these residues on their hands, where the chemical can be absorbed through the skin or ingested when they put their hands in their mouths—and young kids, especially toddlers, put their hands in their mouths a lot. When we redid the calculations, we found that these vulnerable children could be exposed at levels that put their developing brains at risk.83

The exact same exposure pathway (and suite of concerns) exists with regards to pesticide exposure for children and other humans that come into contact with a companion animal wearing a Seresto collar. In fact, when used “in accordance with widespread and commonly recognized practice,” Seresto “gradually releas[es] a consistent low-dose of its active ingredients . . . once the collar comes in contact with your pet’s skin or coat. The active ingredients diffuse into the lipid (fatty/oily) layer of your pet’s skin and fur and cover your pet within 24 hours.”84 Once in place, the collar then “remains effective for eight months at a time,” meaning that the potential for a child or other person to be exposed to its active ingredients (for example, through petting,

Exhibit B (National Pesticide Information Center Reports to EPA); Exhibit C (MedWatch Veterinary Incident Reports). 79 Jonathan Hettinger, Popular Flea Collar Linked to Almost 1,700 Pet Deaths. The EPA Has Issued No Warning, USA Today (Mar. 2, 2021), https://www.usatoday.com/story/news/investigations/2021/03/02/seresto-dog-cat-collars-found-harm- pets-humans-epa-records-show/4574753001/. 80 NRDC, Petition to Cancel All Tetrachlorvinphos (TCVP) Pet Uses (Apr. 23, 2009), https://www.regulations.gov/document/EPA-HQ-OPP-2009-0308-0002. 81 NRDC v. United States EPA (In re NRDC), 956 F.3d 1134, 1136 (9th Cir. 2020). 82 EPA, Tetrachlorvinphos: Animal Incident Summary (Feb. 3, 2009), https://www.documentcloud.org/documents/20491417-epa-hq-opp-2008-0316-0018_pet-poisoning. 83 NRDC, No More Poisons on Pets: The EPA Must Act (May 29, 2019), https://www.nrdc.org/experts/miriam-rotkin-ellman/no-more-poisons-pets-epa-must-act. 84 Advantage Petcare, How Do Seresto Flea Collars Work? (Feb. 2021), https://www.advantagepetcare.com.au/au/parasites/fleas/how-do-seresto-flea-collars-work/. 12 kissing, snuggling, sleeping, or other contact—affections common between people, and especially children, and their companion animals) is also sustained over a long period of time, lasting up to eight months.85 And there can be no question that these impacts on human health are significant here since approximately 700 of the adverse incident reports for Seresto involved harm to humans.86

For the animals themselves, this also means that exposure to the active ingredients in Seresto is chronic since the collar is designed for the consumer to “buy it, put it on and then forget about it for months.”87 For example, while the product label indicates that the collar is for external use only, that direction does not account for the fact that dogs and cats frequently clean themselves (by, for example, licking their fur), and can ingest the collar’s pesticides in so doing. As identified supra in Section III (c), such exposure can lead to a variety of unreasonable and harmful effects in the animals, the significance of which is underscored by the product’s stunning 75,000 adverse incident reports and staggering almost 1,700 pet deaths.

In addition, to the extent animals wearing the Seresto collar are washed or otherwise sluff the collar’s active ingredients into the surrounding environment—for example through rolling or other activities, those active ingredients can come into contact with wildlife, including federally protected threatened and endangered species, and further place those already imperiled species at a greater risk of extinction. For example, as identified supra in Section III (c), uses of imidacloprid are directly implicated in declines of rusty patched bumble bee populations, a species that is listed as endangered under the federal Endangered Species Act.88

Finally, the harms caused by Seresto use are not outweighed by the benefits of continued use because numerous proven effective methods exist for treating fleas and ticks on companion animals that do put the animal’s health, or the health of exposed humans and wildlife, at risk. These alternatives include oral flea-prevention treatments, frequent grooming, and use of nontoxic flea and tick shampoos.89

In sum, considerable evidence exists that past and present uses of the pesticide product Seresto are causing unreasonable adverse impacts on the environment, including “unreasonable risk[s] to man,” companion animals, and threatened and endangered species. Because these harms are significant and ongoing, cancellation of this product is not only warranted by EPA but essential for protecting public health, consumers, imperiled wildlife, and companion animals.

85 Id. 86 See Exhibit A. 87 Id. 88 See, e.g., Szymanski, J. et al. Rusty Patched Bumble Bee (Bombus affinis) Species Status Assessment (2016), https://ecos.fws.gov/ServCat/DownloadFile/120109. 89 See, e.g., NRDC, Nontoxic Ways to Protect Your Pet (Jan. 22, 2016), https://www.nrdc.org/stories/nontoxic-ways-protect-your-pet. 13

b. Immediate Suspension of Seresto’s Registration Pending Cancellation is Warranted

Suspension of a pesticide’s registration is warranted under FIFRA § 136d(c)(1) when such action is necessary to prevent an imminent hazard90 during the time required for cancellation.91 The term "imminent hazard" is defined as "a situation which exists when the continued use of a pesticide during the time required for [a] cancellation proceeding would be likely to result in unreasonable adverse effects on the environment or will involve unreasonable hazard to the survival of a species declared endangered or threatened."92 Here, as documented supra in Sections III(b) – (c) and IV(a), both of these situations exist (ongoing and imminent unreasonable adverse effects on the environment and unreasonable hazard to the survival of the endangered rusty patched bumble bee, as well as other imperiled pollinators).93

Quick action from EPA to remove this product from the market is also a matter of substantial public concern. The significant harms associated with the use of this product have sparked a public outcry,94 retailers considering whether they should discontinue sale of the product,95 and a federal Congressional request to the manufacturer of Seresto to voluntarily recall the collars (the

90 7 U.S.C. § 136(l) (“The term ‘imminent hazard’ means a situation which exists when the continued use of a pesticide during the time required for cancellation proceeding would be likely to result in unreasonable adverse effects on the environment . . . .”). 91 Id. §136d(c)(1) (“If the Administrator determines that action is necessary to prevent an imminent hazard during the time required for cancellation … the Administrator may, by order, suspend the registration of the pesticide immediately.”). 92 Id. § 136(l). 93 See also Envtl. Defense Fund, Inc. v. EPA, 510 F. 2d 1292, 1297 (D.C. Cir. 1975) (upholding an EPA suspension and cancellation order for aldrin and dieldrin and stating: “We have cautioned that the term ‘imminent hazard’ is not limited to a concept of crisis. ‘It is enough if there is a substantial likelihood that serious harm will be experienced during the year or two required in any realized projection of the administrative process.’” (citing Envtl. Defense Fund, Inc. v. EPA, 465 F.2d 528, 540 (D.C. Cir. 1972)); EPA, E.I. du Pont de Nemours and Company Imprelis Order (Aug. 11, 2011), https://www.epa.gov/enforcement/e-i-du-pont-de-nemours-and-company-imprelis-order (EPA order under FIFRA to E.I. DuPont de Nemours (DuPont) directing the company to immediately cease the distribution, sale, use or removal of Imprelis herbicide products under its ownership, control, or custody because “[t]he directions for use and/or warning or caution statements on DuPont’s Imprelis labeling are inadequate to protect non-target species.”). 94 Jonathan Hettinger, Popular Flea Collar Linked to Almost 1,700 Pet Deaths. The EPA Has Issued No Warning, USA Today (Mar. 2, 2021), https://www.usatoday.com/story/news/investigations/2021/03/02/seresto-dog-cat-collars-found-harm- pets-humans-epa-records-show/4574753001/; CBS New York, Questions Raised About Safety of Popular Seresto Flea Collar (Mar. 24, 2021), https://newyork.cbslocal.com/2021/03/24/seresto-pet-collar-safety- concerns/. 95 Jonathan Hettinger, Amazon is Reviewing Best-Selling Seresto Flea Collar After Report of Illnesses, Deaths, USA Today (Mar. 5, 2021), https://www.usatoday.com/story/news/investigations/2021/03/05/amazon-reviewing-seresto-flea-collar- amid-reports-illnesses-deaths/4586990001/. 14 manufacturer declined to do so).96 In furtherance of the public interest and the objectives of FIFRA, the registration for Seresto should, therefore, be suspended pending cancellation proceedings to prevent an imminent hazard to human health and companion animals, and to protect threatened and endangered species.

V. CONCLUSION

For the forgoing reasons, Petitioner the Center for Biological Diversity requests that, pursuant to its obligations under FIFRA, EPA cancel registration number 11556-155 (Seresto) pursuant to Section 136d(b) to prevent additional unreasonable adverse effects on the environment, and, pending completion of cancellation proceedings, suspend Seresto’s registration pursuant to Section 136d(c)(1). As the government agency that has assumed the responsibility of lawfully managing pesticide product registrations in a way that does not harm the environment and human health, EPA can and must do better. The Center urges EPA to act on this petition without delay.

Sincerely,

Hannah M.M. Connor Senior Attorney Center for Biological Diversity P.O. Box 2155 St. Petersburg, FL 33731 Phone: (202) 681-1676 [email protected]

Lori Ann Burd Environmental Health Director Center for Biological Diversity P.O. Box 11374 Portland, OR 97211 Phone: (971) 717-6405 [email protected]

Enclosures

96 Jonathan Hettinger, House Subcommittee Seeks Voluntary Recall of Seresto Flea and Tick Collars, Midwest Center for Investigative Reporting (Mar. 18, 2021), https://investigatemidwest.org/2021/03/18/house-subcommittee-seeks-voluntarily-recall-of-seresto-flea- and-tick-collars/. 15

EXHIBIT A US EPA Office of Pesticide Programs Incident Data System

Total Rows Returned : 48 Aggregate Incident Summary Report by Product Report Date & Time : 06/16/2020 2:46:00 PM GM Reg No. Selected : 011556-00155

Product Name: All Exposure Severity Code : All Reporting Date Range: 01/01/2012 To 06/16/2020

D C O D D G G S S P P Package and Full Product Total H H D D D D D D W P N G G W W W W W W D D Seq. # Reg. # Product Name Form. Inc. D E A B E C D E B B T B C B C B C B C B C 024671-00008 011556-00155 SERESTO CAT Impregnated 10 0 0 0 0 0 0 10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 024968-00005 011556-00155 SERESTO LARGE Impregnated 56 0 0 2 0 0 23 31 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DOG Materials 025109-00007 011556-00155 SERESTO Impregnated 141 2 0 6 0 0 32 101 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 025472-00010 011556-00155 SERESTO Impregnated 944 25 0 19 9 0 222 669 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 025767-00009 011556-00155 SERESTO Impregnated 1,661 13 0 37 90 0 447 1,074 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 026184-00005 011556-00155 SERESTO Impregnated 1,076 15 0 23 101 0 269 668 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 026494-00002 011556-00155 SERESTO Impregnated 602 4 0 17 80 0 161 350 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 026745-00008 011556-00155 SERESTO Impregnated 1,896 25 0 29 90 0 433 1,319 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 027067-00012 011556-00155 SERESTO Impregnated 2,028 30 0 31 159 0 505 1,303 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 027348-00007 011556-00155 SERESTO Impregnated 1,301 19 0 28 98 0 315 841 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 027609-00005 011556-00155 SERESTO Impregnated 775 8 0 20 80 0 197 471 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 027876-00012 011556-00155 SERESTO Impregnated 3,265 39 0 52 133 0 747 2,296 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 028098-00010 011556-00155 SERESTO Impregnated 3,507 24 0 70 273 0 770 2,370 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 028336-00008 011556-00155 SERESTO Impregnated 2,221 15 0 49 229 0 507 1,421 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 028777-00004 011556-00155 SERESTO Impregnated 1,456 20 0 37 125 0 324 950 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 029069-00009 011556-00155 SERESTO Impregnated 4,076 33 0 69 148 0 858 2,970 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 029169-00002 011556-00155 SERESTO LARGE Impregnated 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DOG Materials 029308-00008 011556-00155 SERESTO Impregnated 4,417 26 0 86 309 0 981 3,015 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials

Page 1 of 4 US EPA Office of Pesticide Programs Incident Data System

Total Rows Returned : 48 Aggregate Incident Summary Report by Product Report Date & Time : 06/16/2020 2:46:00 PM GM D C O D D G G S S P P Package and Full Product Total H H D D D D D D W P N G G W W W W W W D D Seq. # Reg. # Product Name Form. Inc. D E A B E C D E B B T B C B C B C B C B C 029600-00007 011556-00155 SERESTO Impregnated 2,488 15 0 54 239 0 600 1,580 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 029843-00005 011556-00155 SERESTO Impregnated 1,697 15 0 54 159 1,118 351 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 030205-00008 011556-00155 SERESTO Impregnated 4,101 34 0 92 208 3,767 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 030491-00009 011556-00155 SERESTO Impregnated 4,564 24 0 87 350 4,103 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 030703-00006 011556-00155 SERESTO Impregnated 3,011 21 0 86 299 2,605 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 030964-00006 011556-00155 SERESTO Impregnated 1,490 18 0 63 157 1,252 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 031245-00008 011556-00155 SERESTO Impregnated 4,381 35 0 12 226 3,995 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 5 031516-00012 011556-00155 SERESTO Impregnated 5,247 40 0 14 102 4,958 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 8 031728-00008 011556-00155 SERESTO Impregnated 3,019 24 0 81 21 2,893 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032053-00003 011556-00155 SERESTO Impregnated 1,669 25 0 70 13 1,561 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032333-00010 011556-00155 SERESTO Impregnated 4,651 44 0 15 30 4,426 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 1 032632-00008 011556-00155 SERESTO Impregnated 31 2 0 2 0 27 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032632-00009 011556-00155 SERESTO Impregnated 1,157 7 0 14 2 1,134 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032632-00010 011556-00155 SERESTO Impregnated 168 4 0 8 2 154 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032632-00011 011556-00155 SERESTO Impregnated 2,511 10 0 24 14 2,463 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032632-00012 011556-00155 SERESTO Impregnated 3 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032632-00013 011556-00155 SERESTO Impregnated 1,476 6 0 4 5 1,461 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032924-00004 011556-00155 SERESTO Impregnated 14 2 0 0 0 12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032924-00005 011556-00155 SERESTO Impregnated 668 5 0 12 3 648 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032924-00006 011556-00155 SERESTO Impregnated 117 5 0 4 0 108 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials 032924-00007 011556-00155 SERESTO Impregnated 1,231 11 0 9 3 1,208 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Materials

Page 2 of 4 US EPA Office of Pesticide Programs Incident Data System

Full Product Reg. # Total Inc. HD HE DA DB DCDE DC DD DE WB PB ONT GB GC DWB DWC GWB GWC SWB SWB PDB PDC 011556-00155 75,385 666 1 1,698 3,767 40,087 7,743 21,439 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Summary by 11 Character Reg. #

11 Char Reg. # Total Inc. HD HE DA DB DCDE DC DD DE WB PB ONT GB GC DWB DWC GWB GWC SWB SWC PDB PDC 011556-00155 75,385 666 1 1,698 3,767 40,087 7,743 21,439 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Exposure Severity Code Description DA Domestic Animal - Fatality DB Domestic Animal - Major DC Domestic Animal - Moderate DCDE Domestic Animal - Moderate, Minor and Unknown DD Domestic Animal - Minor DE Domestic Animal - Unspecified DWB Drinking Water - Moderate

Page 3 of 4 US EPA Office of Pesticide Programs Incident Data System

Total Rows Returned : 48 Aggregate Incident Summary Report by Product Report Date & Time : 06/16/2020 2:46:00 PM GM Exposure Severity Code Description DWC Drinking Water - Minor GB Groundwater - Moderate (with possibly mixed types of water) GC Groundwater - Minor (with possibly mixed types of water) GWB Groundwater - Moderate GWC Groundwater - Minor HD Human - Minor HE Human - Unspecified ONT Other Nontarget PB Plant Damage - Minor PDB Property Damage - Moderate PDC Property Damage - Minor PL Plant Lawn SWB Surface Water - Moderate SWC Surface Water - Minor WB Wildlife - Minor

Page 4 of 4 EXHIBIT B

EXHIBIT C

EXHIBIT D Index to Exhibit D (Petition to Cancel Registration of PNR1427 (Brand Name Seresto) under the Federal Insecticide, Fungicide, and Rodenticide Act; Reg. No. 11556-155)

1. EPA, Notice of Pesticide Registration, Reg. No. 11556-155 (2012), https://www3.epa.gov/pesticides/chem_search/ppls/011556-00155-20120316.pdf. 2. EPA, Weighing Risks to Children from Dogs Wearing Seresto Collars (2016), https://www.epa.gov/sites/production/files/2017- 01/documents/weighing_risks_to_children_from_dogs_wearing_seresto-tm_collars.pdf. 3. EPA, Preliminary Terrestrial Risk Assessment to Support the Registration Review of Imidacloprid, at 11-12 (2017), https://www.regulations.gov/document/EPA-HQ-OPP- 2008-0844-1256. 4. Szymanski, J., et al., Rusty Patched Bumble Bee (Bombus affinis) Species Status Assessment (2016), https://ecos.fws.gov/ServCat/DownloadFile/120109. 5. Jennifer Hopwood, et al., The Xerces Soc’y for Invertebrate Conservation, Are Neonicotinoids Killing Bees?, at vi (2012), http://cues.cfans.umn.edu/old/pollinators/pdf- pesticides/Are-Neonicotinoids-Killing-Bees_Xerces-Society.pdf/. 6. Barraud, A., et al., The Impact of Pollen Quality on the Sensitivity of Bumblebees to Pesticides, 105 Acta Oecologica 103552 (2020). 7. Whitehorn, P. R., et al., Neonicotinoid Pesticide Reduces Bumble Bee Colony Growth and Queen Production, 336 Science 351–352 (2012). 8. Feltham, H., Park, K., Goulson, D., Field Realistic Doses of Pesticide Imidacloprid Reduce Bumblebee Pollen Foraging Efficiency, 23 Ecotoxicology 317–323 (2014). 9. Christoph Sandrock et.al., Sublethal Neonicotinoid Insecticide Exposure Reduces Solitary Bee Reproductive Success, 16 Agricultural & Forest Entomology 119 (2014), https://beyondpesticides.org/assets/media/documents/pollinators/documents/Sandrocketal 2013_Sublethalneonicexposurereducessolitarybeereproductivesuccess_AgricForEnt.pdf. 10. Margaret Eng, et al., Imidacloprid and Chlorpyrifos Insecticides Impair Migratory Ability in a Seed-Eating Songbird, 7 Scientific Reports 15176, DOI:10.1038/s41598-017- 15446-x (2017). 11. Ertl, H. et al., Potential Impact of Neonicotinoid Use on Northern bobwhite (Colinus virginianus) in Texas: A Historical Analysis, PLoS ONE 13:e0191100 (2018), https://doi.org/10.1371/journal.pone.0191100. 12. Millott et al., Field Evidence of Bird Poisonings by Imidacloprid-Treated Seeds: A Review of Incidents Reported by the French SAGIR Network from 1995 to 2014, Environ Sci Pollut Res, DOI 10.1007/s11356-016-8272y (2016). 13. Lopez-Antia et al., Risk Assessment of Pesticide Seed Treatment for Farmland Birds Using Refined Field Data, 136 Environmental Research 97 (2015). 14. EPA, FOIAOnline, Request No. EPA-HQ-2019-004044 (2019), https://foiaonline.gov/foiaonline/action/public/submissionDetails?trackingNumber=EPA- HQ-2019-004044&type=request. 15. NRDC, Neonicotinoid Pesticides: Potential Risks to Brain and Sperm (Jan. 6, 2021), https://www.nrdc.org/experts/jennifer-sass/neonic-pesticides-potential-risks-brain-and-

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sperm#:~:text=Imidacloprid%20is%20the%20most%20common,by%20EPA%20(see%2 0here). 16. EPA, Preliminary Health Effects Division Risk Assessment for Imidacloprid, at 13 (2003), https://www3.epa.gov/pesticides/chem_search/cleared_reviews/csr_PC- 129099_4-Mar-03_111.pdf. 17. EPA, Imidacloprid: Human Health Draft Risk Assessment for Registration Review, at 11-12 (2017), https://www.regulations.gov/document?D=EPA-HQ-OPP-2008-0844- 1235. 18. Cal. EPA, Imidacloprid: Risk Characterization Document; Dietary and Drinking Water Exposure, at ix (2006), https://www.cdpr.ca.gov/docs/risk/rcd/imidacloprid.pdf. 19. Cimino, et al., Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review, 125(2) Environmental Health Perspectives 155 (2017), https://ehp.niehs.nih.gov/doi/full/10.1289/EHP515. 20. Keil, et al., Autism Spectrum Disorder, Flea and Tick Medication, and Adjustments for Exposure Misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) Control Study, 13 Environ. Health 3 (2014), https://pubmed.ncbi.nlm.nih.gov/24456651/. 21. T.G.E. Davies et al., DDT, Pyrethrins, Pyrethroids and Insect Sodium Channels, 59 LIFE 151, 155 (2007). 22. Muhammad M. Hossain, et al., Hippocampal ER Stress and Learning Deficits Following Repeated Pyrethroid Exposure, 143 Toxicological Sciences 220, 220 (2015). 23. Holly A Rogers, et al., Bifenthrin Causes Trophic Cascade and Altered Insect Emergence in Mesocosms: Implications for Small Streams, 50 Envtl. Sci. & Tech. 11,974, 11,974 (2016). 24. Stephen J. Godin, et al., Physiologically Based Pharmacokinetic Modeling of Deltamethrin: Development of a Rat and Human Diffusion-Limited Model, 115 Toxicological Sciences 330, 338 (2010). 25. Janie F. Shelton, et al. Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study, 122 Children’s Health 1103, 1107 (2014). 26. EPA, Flumethrin: Human Health Risk Assessment for the Section 3 Registration Action for Cat and Dog Collars (2016), https://www.regulations.gov/document?D=EPA-HQ- OPP-2016-0031-0005. 27. EPA, Flumethrin: Draft Human Health Risk Assessment for Registration Review (2018), https://www.regulations.gov/document?D=EPA-HQ-OPP-2016-0031-0027. 28. EPA, Flumethrin: Tier I Update Review of Humane Incidents and Epidemiology for Proposed Interim Decision, at 3-4 (2019), https://www.regulations.gov/document/EPA- HQ-OPP-2016-0031-0031. 29. Holly A Rogers, et al., Bifenthrin Causes Trophic Cascade and Altered Insect Emergence in Mesocosms: Implications for Small Streams, 50 Envtl. Sci. & Tech. 11,974, 11,974 (2016). 30. EPA, Preliminary Comparative Environmental Fate and Ecological Risk Assessment for the Registration Review of Eight Synthetic Pyrethroids and the Pyrethrins, (2016), https://www.regulations.gov/document/EPA-HQ-OPP-2010-0384-0045. 31. Nathan Donley, Center for Biological Diversity, Toxic Concoctions: How the EPA Ignores The Dangers of Pesticide Cocktails, 1 (2016),

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https://www.biologicaldiversity.org/campaigns/pesticides_reduction/pdfs/Toxic_concocti ons.pdf. 32. Stanneck, et al., The Synergistic Action of Imidacloprid and Flumethrin and Their Release Kinetics From Collars Applied for Ectoparasite Control in Dogs and Cats, 5 Parasites & Vectors 73 (2012), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361670/. 33. Schulz, Applied Pesticide Toxicity Shifts Toward Plants and Invertebrates, Even in GM Crops, 372 Science 81-84 (2021), https://science.sciencemag.org/content/372/6537/81. 34. Marc Heller, Farm Chemicals Turning More Toxic for Wildlife, E&E News (Apr. 1, 2021), https://www.eenews.net/eenewspm/stories/1063729071/feed. 35. Jimy Tallal, Seresto Flea Collar Linked to 1,700 Pet Deaths, The Malibu Times (Mar. 26, 2021), http://www.malibutimes.com/news/article_36818990-8db8-11eb-9bf9- cf20318319cf.html. 36. Jonathan Hettinger, Popular Flea Collar Linked to Almost 1,700 Pet Deaths. The EPA Has Issued No Warning, USA Today (Mar. 2, 2021), https://www.usatoday.com/story/news/investigations/2021/03/02/seresto-dog-cat-collars- found-harm-pets-humans-epa-records-show/4574753001/. 37. NRDC, Petition to Cancel All Tetrachlorvinphos (TCVP) Pet Uses (Apr. 23, 2009), https://www.regulations.gov/document/EPA-HQ-OPP-2009-0308-0002. 38. EPA, Tetrachlorvinphos: Animal Incident Summary (Feb. 3, 2009), https://www.documentcloud.org/documents/20491417-epa-hq-opp-2008-0316-0018_pet- poisoning. 39. NRDC, No More Poisons on Pets: The EPA Must Act (May 29, 2019), https://www.nrdc.org/experts/miriam-rotkin-ellman/no-more-poisons-pets-epa-must-act. 40. Advantage Petcare, How Do Seresto Flea Collars Work? (Feb. 2021), https://www.advantagepetcare.com.au/au/parasites/fleas/how-do-seresto-flea-collars- work/. 41. NRDC, Nontoxic Ways to Protect Your Pet (Jan. 22, 2016), https://www.nrdc.org/stories/nontoxic-ways-protect-your-pet. 42. EPA, E.I. du Pont de Nemours and Company Imprelis Order (Aug. 11, 2011), https://www.epa.gov/enforcement/e-i-du-pont-de-nemours-and-company-imprelis-order. 43. CBS New York, Questions Raised About Safety of Popular Seresto Flea Collar (Mar. 24, 2021), https://newyork.cbslocal.com/2021/03/24/seresto-pet-collar-safety-concerns/. 44. Jonathan Hettinger, Amazon is Reviewing Best-Selling Seresto Flea Collar After Report of Illnesses, Deaths, USA Today (Mar. 5, 2021), https://www.usatoday.com/story/news/investigations/2021/03/05/amazon-reviewing- seresto-flea-collar-amid-reports-illnesses-deaths/4586990001/ 45. Jonathan Hettinger, House Subcommittee Seeks Voluntary Recall of Seresto Flea and Tick Collars, Midwest Center for Investigative Reporting (Mar. 18, 2021), https://investigatemidwest.org/2021/03/18/house-subcommittee-seeks-voluntarily-recall- of-seresto-flea-and-tick-collars/.

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